ESK-001 / Alumis - LARVOL DELTA

An Investigational Study of ESK-001 in Participants With Normal Liver Function and Participants With Mild, Moderate, and Severe Liver Damage (clinicaltrials.gov) - P1 | N=48 | Recruiting | Sponsor: Alumis Inc

New P1 trial • Hepatology

Alumis and ACELYRIN Announce Amended Merger Agreement (GlobeNewswire) - "Merger maximizes the potential value for ACELYRIN stockholders and creates a stronger combined company, best-positioned to realize long-term value of multiple late-stage assets...Alumis Inc...and ACELYRIN, INC...announced an amendment to the existing terms of their previously announced merger agreement...Under the terms of the amended agreement, ACELYRIN stockholders will now receive 0.4814 shares of Alumis common stock for each share of ACELYRIN common stock owned, representing a meaningful increase in the ownership percentage of the combined company over the original definitive merger agreement....'We continue to believe that this combination is the most value-maximizing path forward for ACELYRIN stockholders and that Alumis is the right partner to optimize development of lonigutamab.'"

M&A • Immunology • Multiple Sclerosis • Systemic Lupus Erythematosus • Thyroid Eye Disease

Alumis and ACELYRIN File Joint Definitive Proxy Statement for Proposed Merger (GlobeNewswire) - "Alumis Inc...and ACELYRIN, INC...have jointly filed a definitive proxy statement/prospectus with the U.S. Securities and Exchange Commission in connection with the proposed merger of the two companies. The joint proxy statement/prospectus are being mailed to all Alumis and ACELYRIN stockholders entitled to vote...Topline data from Phase 2b LUMUS trial in systemic lupus erythematosus on track for readout in 2026; Phase 2 clinical trial initiation for Alumis’ A-005 in MS...Pro forma cash of approximately $737 million as of December 31, 2024, provides runway into 2027, beyond multiple expected clinical readouts....By combining assets, resources and talent, including members of ACELYRIN’s lonigutamab program, the combined company will be well positioned to maximize the value of its pipeline."

M&A • New P2 trial • P2b data • Multiple Sclerosis • Systemic Lupus Erythematosus • Thyroid Eye Disease

Alumis and Kaken Pharmaceutical Announce Collaboration and Licensing Agreement for ESK-001 in Dermatology in Japan (GlobeNewswire) - "Alumis Inc...and Kaken Pharmaceutical Co., Ltd...announced that the companies have entered into a collaboration and licensing agreement to develop, manufacture and commercialize ESK-001, a highly selective, next-generation oral tyrosine kinase 2 (TYK2) inhibitor, for dermatology indications in Japan, with the option to expand the license to include rheumatological and gastrointestinal diseases...Under the terms of the agreement, Alumis will receive $40 million in upfront and near-term co-development payments in 2025 to 2026, with the potential to earn up to approximately $140 million in additional payments based on the achievement of milestones, and field option payments. Alumis is also eligible to receive tiered royalties ranging from the low double-digits into the twenties on aggregate net sales of ESK-001 in Japan. Kaken will be responsible for the clinical development, regulatory approvals and commercialization of ESK-001 in Japan, and Alumis will retain rights to..."

Licensing / partnership • Psoriasis • Systemic Lupus Erythematosus

Alumis Reports Year End 2024 Financial Results and Highlights Recent Achievements (GlobeNewswire) - "Upon the close of the transaction, Alumis stockholders will own approximately 55% of the combined company and ACELYRIN stockholders will own approximately 45% of the combined company, on a fully diluted basis....Closing of merger transaction with ACELYRIN (2Q 2025)....Research and development expenses were $265.6 million for the year ended December 31, 2024, compared to $137.7 million for the year ended December 31, 2023. The increase was driven by a clinical milestone payment of $23.0 million related to the prior acquisition of FronThera, an increase in contract research and manufacturing and clinical trial costs for the ESK-001 and A-005 programs..."

M&A • Multiple Sclerosis • Psoriasis • Systemic Lupus Erythematosus

Alumis and ACELYRIN Reaffirm Strategic and Financial Rationale of Proposed Merger (GlobeNewswire) - "A combined, differentiated late-stage portfolio of therapies and increased resources enabling the development of life-changing medicines. The combined company will have a diversified portfolio of late-stage clinical assets for validated targets that are set to meaningfully change the treatment paradigm for patients in large, well-established multi-billion dollar markets. These programs, including ESK-001 in moderate-to-severe plaque psoriasis and systemic lupus erythematosus, lonigutamab for thyroid eye disease, and A-005 in multiple sclerosis, offer multiple, high-value catalysts that can be achieved with the financial resources of the combined company...Alumis and ACELYRIN had cash, cash equivalents and marketable securities of approximately $289 million and approximately $448 million, respectively, on a preliminary basis, as of December 31, 2024."

M&A • Multiple Sclerosis • Psoriasis • Systemic Lupus Erythematosus • Thyroid Eye Disease

Late-Breaking ESK-001 Phase 2 OLE Data Presented at 2025 AAD Annual Meeting Demonstrate Robust Clinical Responses Over 52-Weeks in Psoriasis (GlobeNewswire) - P2 | N=165 | NCT05739435 | Sponsor: Alumis Inc | "These data demonstrated that patients receiving 40 mg twice daily dosing of ESK-001 achieved long-term sustained or increasing clinical responses through Week 52 compared to Week 12 (using modified non-responder imputation, n=80) as measured by PASI 90 (61.3% vs. 52.4%), PASI 100 (38.8% vs. 26.8%), and sPGA 0 (38.8% vs. 32.9%). At Week 52, patients maintained robust clinical improvements in control of itch (NRS≤4, 81.3%) and quality-of-life (DLQI0/1, 61.3%). Treatment with ESK-001 continued to be generally well tolerated at week 52, with safety and tolerability consistent with previously reported Week 16 and Week 28 data and no new safety findings."

Late-breaking abstract • P2 data • Psoriasis

Patient-Reported Outcomes in the Phase 2 Studies of ESK-001, an Oral Allosteric TYK2 Inhibitor, in Adults with Moderate-to-Severe Plaque Psoriasis (AAD 2025) - P2 | "ESK-001 was generally safe and well tolerated in both STRIDE and the OLE. No deaths, treatment related AEs associated with the JAK inhibitor class, or clinically significant laboratory or ECG trends were observed."

Clinical • P2 data • Patient reported outcomes • Dermatology • Immunology • Pruritus • Psoriasis • TYK2

Pharmacokinetics, Safety, and Tolerability of ESK-001, an Allosteric TYK2 Inhibitor for Plaque Psoriasis: Evaluation in Asian Populations Compared to Caucasians (AAD 2025) - "No clinically relevant differences in PK parameters, safety, or tolerability were observed across ethnicities, supporting the conclusion that the same therapeutic dosing regimen can be safely used for psoriasis treatment in these populations."

Clinical • PK/PD data • Dermatology • Immunology • Psoriasis • TYK2

ESK-001, an allosteric TYK2 inhibitor, modulates disease and TYK2-related pathway transcriptomic and proteomic biomarkers in Psoriasis STRIDE trial patients (AAD 2025) - "Patients with high intrinsic IL23 pathway expression were most likely to achieve high and rapid PASI response in the dose group with maximal target engagement (40mg BID) compared to those with low expression. Disease-relevant transcriptomic analysis in skin indicates a return of key psoriasis biomarkers to non-lesional baseline levels."

Biomarker • Clinical • Dermatology • Immunology • Psoriasis • IL17A • IL22 • TYK2

Efficacy and safety of ESK-001, a highly selective oral TYK2 inhibitor, in moderate-to-severe plaque psoriasis: long term Phase 2 results (AAD 2025) - No abstract available

Clinical • Late-breaking abstract • P2 data • Dermatology • Immunology • Psoriasis • TYK2

Alumis Announces Late-Breaker Psoriasis Presentation of 52-week Phase 2 OLE Data for ESK-001 at 2025 American Academy of Dermatology Annual Meeting and Accelerated Topline Phase 3 Data Readout (GlobeNewswire) - "Late-breaking oral presentation to highlight 52-week data of ESK-001 in a Phase 2 open-label extension (OLE) study in adults with moderate-to-severe plaque psoriasis; Additional Phase 2 e-poster presentations to describe patient-reported outcomes, disease biomarker activity and pharmacokinetic data of ESK-001 in psoriasis patients; Phase 3 ONWARD program topline data now expected in Q1 2026."

P2 data • P3 data: top line • Psoriasis

ONWARD3: Long-term Safety and Efficacy of ESK-001 in Moderate to Severe Plaque Psoriasis (clinicaltrials.gov) - P3 | N=1680 | Recruiting | Sponsor: Alumis Inc

New P3 trial • Dermatology • Immunology • Psoriasis

Combined Pipeline (GlobeNewswire) - "(i) ESK-001:...Alumis expects a Phase 2 OLE 52-week data update in PsO in 2025, Phase 3 topline data for PsO in the first half of 2026 and Phase 2b topline data for SLE in 2026...; (ii) A-005:... Alumis expects initiation of its Phase 2 clinical trial in MS in the second half of 2025 with Phase 2 topline data expected in 2026."

New P2 trial • P2 data • P3 data: top line • Multiple Sclerosis • Psoriasis • Systemic Lupus Erythematosus

Alumis and ACELYRIN to Merge Creating a Late-Stage Clinical Biopharma Company Dedicated to Innovating, Developing and Commercializing Transformative Therapies for Immune-mediated Diseases (GlobeNewswire) - "Alumis...and ACELYRIN...announced a definitive merger agreement under which Alumis and ACELYRIN will merge in an all-stock transaction....The combined company will benefit from a differentiated late-stage portfolio of therapies and increased resources enabling the development of life-changing medicines....Under the terms of the agreement, ACELYRIN stockholders will receive 0.4274 shares of Alumis common stock for each share of ACELYRIN common stock owned. Upon the close of the transaction, Alumis stockholders will own approximately 55% of the combined company and ACELYRIN stockholders will own approximately 45% of the combined company, on a fully diluted basis."

M&A • Multiple Sclerosis • Parkinson's Disease • Psoriasis • Systemic Lupus Erythematosus • Thyroid Eye Disease

Safety, tolerability, pharmacokinetics, and pharmacodynamics of the oral allosteric TYK2 inhibitor ESK-001 using a randomized, double-blind, placebo-controlled study design. (PubMed, Clin Transl Sci) - "In conclusion, ESK-001 was generally safe and well-tolerated in healthy participants, showed linear dose-dependent PK characteristics, and maximally inhibited TYK2-dependent pathways with a predictable concentration-dependent PK/PD relationship. These findings were used to select the dose range of ESK-001 for the STRIDE phase II trial in plaque psoriasis and to support further clinical development of ESK-001 in other TYK2-mediated diseases."

Clinical • Journal • PK/PD data • Dermatology • Immunology • Psoriasis • SIGLEC1 • TYK2

LUMUS: Phase 2 Placebo-Controlled Study to Assess the Safety and Efficacy of ESK-001 in Active Systemic Lupus Erythematosus (clinicaltrials.gov) - P2 | N=388 | Recruiting | Sponsor: Alumis Inc | Trial completion date: Dec 2025 ➔ Sep 2027 | Trial primary completion date: May 2025 ➔ Jul 2026

Trial completion date • Trial primary completion date • Immunology • Inflammatory Arthritis • Lupus • Systemic Lupus Erythematosus

ESK-001, an Allosteric TYK2 Inhibitor, Maximally Suppresses Type 1 Interferon, a Therapeutic Pathway Central to SLE and CLE (ACR Convergence 2024) - "The STRIDE study undertook transcriptomic analyses in blood and skin to characterize ESK-001's ability to down regulate cytokine pathways such as type I interferons that signal through TYK2 and are thought to be central to SLE/CLE pathogenesis. Public Expression Data: Data from the following series accessions from Gene Expression Omnibus (GEO) were used for analysis: GSE109248, GSE110169, GSE112087, and GSE154851. ESK-001 is a selective TYK2 inhibitor that demonstrates dose-dependent suppression of key pathways that are dysregulated in SLE. Blood RNA-seq shows maximal inhibition of of pathways believed to be central to the pathophysiology of SLE such as type 1 IFN gene expression signatures at the ESK-001 40 mg BID dose. Type 1 IFN was also suppressed in the skin at the top 40mg BID dose."

Dermatology • Immunology • Inflammatory Arthritis • Psoriasis • IFI27 • IFIT1 • LY6E • MX1 • RSAD2 • TYK2

Alumis Presents Data Highlighting ESK-001’s Potential as a High-efficacy Oral Treatment for Systemic Lupus Erythematosus (SLE) at ACR Convergence 2024 (GlobeNewswire) - "Alumis...today announced the company will give two data presentations at ACR Convergence 2024, the annual meeting of the American College of Rheumatology (ACR), being held November 14–19, 2024, in Washington, D.C. Data to be presented at ACR show that treatment with ESK-001, a highly selective allosteric oral tyrosine kinase 2 (TYK2) inhibitor, suppresses both a novel disease biomarker as well as Type 1 interferons, known key drivers of SLE....Data to be presented at ACR show that treatment with ESK-001, a highly selective allosteric oral tyrosine kinase 2 (TYK2) inhibitor, suppresses both a novel disease biomarker as well as Type 1 interferons, known key drivers of SLE. Additionally, leveraging its proprietary data analytics platform, Alumis identified novel pathways implicated in SLE that can be suppressed through TYK2 inhibition."

Biomarker • Clinical data • Lupus • Systemic Lupus Erythematosus

Alumis Reports Third Quarter 2024 Financial Results and Highlights Recent Achievements (GlobeNewswire) - "The Phase 2b LUMUS program for ESK-001 in SLE is designed to evaluate the efficacy, safety and pharmacokinetics of multiple doses of ESK-001 in adult patients with moderately to severely active, autoantibody-positive SLE. Topline results are anticipated in 2026."

P2b data • Systemic Lupus Erythematosus

Late-Breaking Data at EADV of ESK-001, an Oral TYK2 Inhibitor for the Treatment of Psoriasis, Demonstrate Significant Responses with Sustained Increases Over 28 Weeks in Phase 2 OLE Study (GlobeNewswire) - P2 | N=165 | NCT05739435 | Sponsor: Alumis Inc | "Alumis Inc...today announced positive 28-week data from the open-label extension (OLE) period of its Phase 2 STRIDE clinical trial of ESK-001. These data were presented during a late-breaking oral session at the 2024 European Academy of Dermatology & Venereology (EADV) Congress held September 25-29 in Amsterdam, Netherlands....The interim 28-week OLE data (as of March 1, 2024) showed dose-dependent sustained increases in Psoriasis Area and Severity Score (PASI) endpoint responses observed over time, with the majority of patients (93% as observed (AO, n=71), 82.7% using modified non-responder imputation (mNRI, n=81)) achieving PASI 75, the primary endpoint, at the highest dose of 40 mg twice daily."

Late-breaking abstract • P2 data • Immunology • Psoriasis

Efficacy and safety of ESK-001, a highly selective oral TYK2 inhibitor, in moderate-to-severe plaque psoriasis: Phase 2 results through week 28 (EADV 2024) - P2 | "In STRIDE and OLE, Phase 2 studies in patients with moderate-to-severe plaque psoriasis, the oral selective TYK2 inhibitor ESK-001 demonstrated clear dose-dependent efficacy. At the highest dose, 40 mg BID, maximal clinical responses were safely achieved at Week 28. Indirect comparisons of historical data suggest that ESK-001 has the potential for best-in-class efficacy, with efficacy in the range reported for many biologic therapies for psoriasis."

Clinical • Late-breaking abstract • P2 data • Dermatology • Immunology • Infectious Disease • Pain • Psoriasis • IL17A • IL23A • TYK2

Exploratory Exposure Response (E-R) Analysis of ESK-001, An allosteric oral TYK2 inhibitor, in Patients with Psoriasis (EADV 2024) - P2 | "The popPK analysis indicated similar exposures and linear PK in both HV and patients with PsO. The E-R analysis revealed a strong positive correlation between exposure and the key efficacy endpoints. Also, there was a positive correlation between time on treatment and the key efficacy endpoints."

Clinical • Dermatology • Immunology • Psoriasis • TYK2

Patient-Reported Outcomes in the Randomized, Double Blind Phase 2 Study of ESK-001, an Oral Allosteric TYK2 Inhibitor, in Adults with Moderate-to-Severe Plaque Psoriasis (EADV 2024) - P2 | "In these Phase 2 moderate-to-severe psoriasis studies ESK-001 demonstrated significant improvements in patient reported quality of life (DLQI) and psoriasis-associated pruritus (NRS) , with a clear dose- dependent improvement observed. Improvements in PROs were maintained with ongoing treatment in the OLE study. These PRO outcomes highlight the positive impact on the lives of patients with psoriasis, while receiving ESK-001."

Clinical • P2 data • Patient reported outcomes • Dermatology • Immunology • Pruritus • Psoriasis • TYK2

ESK-001, an allosteric TYK2 inhibitor, modulates disease and TYK2-related pathway transcriptomic biomarkers in Psoriasis STRIDE trial patients (EADV 2024) - "RNA-Seq of blood and skin biopsies demonstrated that ESK-001 inhibited its target in a dose dependent fashion, with maximum inhibition of disease and TYK2 relevant pathways at the 40 mg BID dose. Disease-relevant transcriptomic analyses indicate a return of key psoriasis biomarkers to non-lesional baseline levels. These effects are in line with biomarker data previously reported by high-efficacy biologics such as secukinumab."

Biomarker • Clinical • CNS Disorders • Dermatology • Immunology • Inflammatory Arthritis • Lupus • Multiple Sclerosis • Psoriasis • Psoriatic Arthritis • Rheumatology • Seronegative Spondyloarthropathies • Systemic Lupus Erythematosus • IL17A • TYK2